Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• trifluoromethylated derivatives play a major role in chemistry [28], their more lipophilic analogues – C2F5 [1][29][30] and SF5 [1][31] – only gain popularity. The C2F5-substituted derivatives, for example, often have higher activity compared with the CF3-counterparts [32][33]. Therefore, some bioactive compounds

• alkynes 1–12 with C2F5CHN2 gives 3,5-disubstituted ones. Also, alkaline hydrolysis of the ester group in 1a gave acid 25 – potential building blocks for medicinal chemistry and drug discovery: many bioactive compounds, including the insecticidal agent DP-23, contain the residue of the CF3-analogue of 25

• layer was separated. The aqueous layer was washed with CH2Cl2 (2 × 3 mL). The combined organic layers were dried over Na2SO4 and evaporated under vacuum to provide the pure product. Bioactive compounds and agrochemicals with fluorinated pyrazoles. Bioactive compounds with C2F5 group [34][35][36]. X-ray

A one-pot multistep cyclization yielding thiadiazoloimidazole derivatives

• Debabrata Samanta,
• Anup Rana,
• Jan W. Bats and
• Michael Schmittel

Beilstein J. Org. Chem. 2014, 10, 2989–2996, doi:10.3762/bjoc.10.317

• bioactive compounds. For instance, thiadiazole containing heterocycles are known to exhibit important anti-inflammatory, antihypertensive, anti-HIV and antituberculosis activity [1]. Within this family, 1,2,4-thiadiazoles display notable medicinal properties as potent neuroprotectors [2

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• of a variety of polycyclic structures containing typical structural elements of bioactive compounds [82]. Since 73 provides manifold possibilities for structural modifications, the generation of complex and structurally diverse scaffolds could be achieved in very few steps (diversity-oriented

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• the corresponding biologically active compounds. These were used as raw mixtures (e.g., extracts for food supplements), as well as purified bioactive compounds for the treatment of various diseases. They were used in natural form or after derivatization to a more bioactive compound, such as the

• compounds. One of the most frequently used matrices for molecular encapsulation, protection against oxidation or other degradation processes, as well as controlled release of relatively small bioactive compounds, are cyclodextrins (CDs) [30][31][32][33][34][35]. These are cyclic oligosaccharides consisting

• small hydrophobic molecules and allow for an increased apparent aqueous solubility of nanoencapsulated bioactive compounds. Moreover, the access of oxygen or other oxidative agents to these bioactive compounds can be reduced. Essential oil components are some of the most appropriate molecules for

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• pharmaceutical compounds [1][2][3][4][5]. In particular, tetracyclic compounds containing the indole substructure represent an important structural motif in a variety of bioactive compounds, such as antitumor agents A [6] and antifungal agents B [7] (Figure 1). Therefore, it is necessary to develop efficient and

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• synthesis of bioactive compounds and natural products. At the end of the century, Lu and co-workers discovered the nucleophilic phosphine-catalyzed [3 + 2] annulation of allenes with electron-deficient imines and established a reasonable reaction mechanism [58][59][60]. Its asymmetric version, however, did

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• bioactive compounds adopting phosphonamide anion technology is presented highlighting the utility of phosphonamide reagents in stereocontrolled bond-forming reactions. Methodologies utilizing phosphonamide anions in asymmetric alkylations, Michael additions, olefinations, and cyclopropanations will be

• products and bioactive compounds discussed in this review. Phosphonamides by Arbuzov reaction An example for the application of the Arbuzov reaction is the synthesis of phosphonamide (R,R)-28a. Thus, heating of (R,R)-N,N’-dimethyl-1,2-diaminocyclohexane (58) with hexamethylphosphorus triamide gave the

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) . Keywords: aminohalogenation; diamination; α,β-diamino ester; one-pot; stereoselectivity; Introduction α,β-Diamino acid derivatives are one of the most important classes of nitrogen-containing bioactive compounds [1][2

Expedient synthesis of 1,6-anhydro-α-D-galactofuranose, a useful intermediate for glycobiological tools

• Luciana Baldoni and
• Carla Marino

Beilstein J. Org. Chem. 2014, 10, 1651–1656, doi:10.3762/bjoc.10.172

• complex products and bioactive compounds. Among the glycosans, the anhydro sugars involving the anomeric center in the ring formation, the 1,6-anhydro sugars are the most common and useful building blocks [1][2]. They can play a role in synthetic methodologies aiming at the obtainment of regioselectively

4-Hydroxy-6-alkyl-2-pyrones as nucleophilic coupling partners in Mitsunobu reactions and oxa-Michael additions

• Michael J. Burns,
• Thomas O. Ronson,
• Richard J. K. Taylor and
• Ian J. S. Fairlamb

Beilstein J. Org. Chem. 2014, 10, 1159–1165, doi:10.3762/bjoc.10.116

• find use in the synthesis of natural products and other bioactive compounds. Experimental General procedure 1: Mitsunobu reaction with 4-hydroxy-2-pyrones: To a stirred solution of the pyrone (1 equiv), triphenylphosphine (1.5 equiv) and alcohol (1.5 equiv), in dichloromethane (4 mL mmol−1) under

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• acetates with azodicarboxylates in the presence of PPh3 (Mitsunobu reaction conditions), which gives an efficient access to α-alkylidene-β-hydrazino acid derivatives, an important precursor for many bioactive compounds [25][26][27][28][29][30] including β-amino acids [25] (Scheme 1, top). However, the

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• as a powerful tool for the synthesis of medium-sized libraries of bioactive compounds. Thus, straightforward syntheses of 1,3-disubstituted-1,2-dihydroisoquinolines have been achieved by three-component reactions between alkynylbenzaldehydes 25 (γ-carbonylalkyne), primary amines 26 (mainly anilines

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• Abstract A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis

• other bioactive compounds [1][2][3][4][5][6][7]. Selected examples are given in Figure 1: The non-peptidic human neurokinin-1 (NK1) substance P receptor antagonists L-733,060 [15][16] and CP-99,994 [17][18][19], the natural product febrifugine (antimalarial) [20][21] and antiprotozoal agent halofuginone

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• , the bark of C. decandra have been used for the treatment of amoebiasis, diarrhea, hemorrhage, and malignant ulcers [5], making it rewarding to screen the bioactive compounds of this plant. Before our work, already 28 compounds had been isolated from C. decandra [6] (three pimaranes, four beyeranes

Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide

• Yuzo Nakamura,
• Motohiro Fujiu,
• Tatsuya Murase,
• Yoshimitsu Itoh,
• Hiroki Serizawa,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2013, 9, 2404–2409, doi:10.3762/bjoc.9.277

• , biological, and physical properties [1][2][3][4][5][6]. Particularly, trifluoromethylated compounds can be widely employed as one of the most effective analogues of bioactive compounds, because the trifluoromethyl group enhances the metabolic stability, lipophilicity, and bioavailability of these compounds

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• [1]. Isocyanates play a relevant role as chemical intermediates in the manufacturing of thermoplastic foams, elastomers, adhesives, agrochemicals and pharmaceuticals. The isocyanate group is also widely used as a precursor to several bioactive compounds and drugs that contain urea and carbamate

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• alkaloids are highly bioactive compounds [167][168]. The diverse spectrum includes vasodilatoring, anti-arrhythmic, immunomodulating and analgesic activities. Hetisines can be classified, according to Wang and Liang, as C20-diterpenoid alkaloids, which belong to the family of atisane alkaloids [167]. The

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• successful in the case of the more complex drug 8-methoxypsoralen (8-MOP). Keywords: alkynylation; benzofurans; cooperative catalysis; direct functionalization; gold catalysis; hypervalent iodine; Introduction Benzofurans are important heterocycles frequently encountered in both bioactive compounds and

• [1][2][3][4]. The natural product coumestrol (4) is found especially in soy beans and has estrogenic activity [5]. Synthetic bioactive compounds containing benzofurans are also important, as exemplified by amiodarone (5), as antiarrythmic drug [6][7]. Finally, benzofurans have also emerged recently

• silica gel and purified directly by column chromatography. Benzofurans in bioactive compounds and materials. Zinc–gold catalyzed C2-alkynylation of benzofurans. Scope of the reaction. Alkynylation of 7-methoxybenzofuran (7j) [31]. Alkynylation of 8-methoxypsoralen (2). Optimization of the alkynylation of

Palladium(II)-catalyzed Heck reaction of aryl halides and arylboronic acids with olefins under mild conditions

• Tanveer Mahamadali Shaikh and
• Fung-E Hong

Beilstein J. Org. Chem. 2013, 9, 1578–1588, doi:10.3762/bjoc.9.180

• Substituted olefins are important structural motifs in natural products, pharmaceuticals, bioactive compounds and organic materials [1][2]. Olefins such as stilbene derivatives normally show antitumor [3], antiinflammatory [4], neuroprotective [5], and cardioprotective [6] properties. Due to its importance in

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• skeleton is frequently used as a pharmacophore for the modification of known pharmaceuticals. Triazole analogues of several bioactive compounds have recently been reported. Examples are those of the well-known highly functionalized antiviral cyclic amino acid derivatives oseltamivir and zanamivir (5 and 6

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• procedure allows the preparation of heterocycles with good yields and is tolerant to a wide variety of functional groups. Keywords: benzofuran; bimetallic catalyst; heterogeneous catalysis; indole; water; Introduction Heterocycles are ubiquitous building blocks in natural products, bioactive compounds and

Catalytic asymmetric tandem Friedel–Crafts alkylation/Michael addition reaction for the synthesis of highly functionalized chromans

• Jiahuan Peng and
• Da-Ming Du

Beilstein J. Org. Chem. 2013, 9, 1210–1216, doi:10.3762/bjoc.9.137

• -linked bis(oxazoline)-Zn(II) complexes. On the other hand, indole and its derivatives are one of the most intensively investigated classical heterocycles owing to their prevalence in bioactive compounds. Indoles have been successfully utilized in asymmetric Friedel–Crafts reactions with nitroolefin and

Short synthesis of the common trisaccharide core of kankanose and kankanoside isolated from Cistanche tubulosa

• Goutam Guchhait and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2013, 9, 705–709, doi:10.3762/bjoc.9.80

• . tubulosa), an Orobanchaceae parasitic plant found in Africa, Asia and Arabia, has been traditionally used as folk medicine and tonic for the treatment of blood-circulation-related disorders, impotence, sterility and body weakness [1][2][3]. A significant number of bioactive compounds have been isolated

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• of various bioactive compounds that possess antibiotic, anti-inflammatory, antimicrobial [5], antidiabetic [6], and antiviral activity against retroviruses including HIV [7]. In addition, quinoxaline derivatives are also associated with a wide spectrum of biological effects including anticancer [8

N-Heterocyclic carbene–palladium catalysts for the direct arylation of pyrrole derivatives with aryl chlorides

• Ismail Özdemir,
• Nevin Gürbüz,
• Nazan Kaloğlu,
• Öznur Doğan,
• Murat Kaloğlu,
• Christian Bruneau and
• Henri Doucet

Beilstein J. Org. Chem. 2013, 9, 303–312, doi:10.3762/bjoc.9.35

• conversion of the aryl chloride. The solvent was removed by heating of the reaction vessel under vacuum and the residue was charged directly onto a silica-gel column. The products were eluted by using an appropriate ratio of diethyl ether and pentane. Examples of pyrrole-containing bioactive compounds